EyeWorld Asia-Pacific March 2015 Issue

51 EWAP CORNEA March 2015 by Lauren Lipuma EyeWorld Staff Writer Study identifies changes to the material properties of the cornea after crosslinking A recent study has shown that corneal collagen crosslinking induces distinct material property changes in the cornea, providing insights into the molecular mechanisms behind the popular procedure. George O. Waring IV, MD , FACS , director of refractive surgery, Storm Eye Institute, Medical University of South Carolina (MUSC), Charleston, and adjunct assistant professor of bioengineering, Clemson University, Clemson, S.C., presented the pilot data from his ocular biomechanics and diffusion lab at the 2014 ASCRS• ASOA Symposium & Congress. With interest in crosslinking on the rise, potential applications for the procedure are extending beyond keratoconus and ectactic disorders. New thoughts about using crosslinking as a refractive procedure—either alone or in conjunction with another treatment—illuminate the need to fully understand its effect on the cornea. “Crosslinking is part of the conversation now, but there are still a lot of unknowns around the exact mechanisms and the precise effect on the cornea,” said Dr. Waring. A collaborative effort between MUSC and the Clemson Department of Bioengineering, Dr. Waring’s research aims to characterize the material and mechanical property changes associated with crosslinking in order to give physicians a better understanding of how crosslinking affects the tissue and where its effects are most pronounced. Clinicians can use this data to optimize the crosslinking procedure and determine the safety and efficacy of different techniques and modifications of the procedure. Methodology “Sophisticated collagen material property analyses have been utilized elsewhere in the body, and we repurposed these methods for understanding the behavior of collagen in the eye, specifically in the cornea,” Dr. Waring said. Their goal was to develop a successful model that can be used to examine these properties under a variety of conditions. In these pilot experiments, the researchers evaluated the effect of crosslinking on ion transport and electrical conductivity of the corneal stroma. Dr. Waring’s team aimed to study these properties in a regional-specific way—across the cornea in the nasal-temporal (x) and superior- inferior (y) directions as well as through the cornea in the anterior-posterior (z) direction. “This is a non-destructive ex vivo method for quantifying and comparing the crosslink effect relative to the stromal depth,” he said. Views from Asia-Pacific Colin CHAN, MD Associate Professor, Vision Eye Institute and University of New South Wales Level 3 270 Victoria Avenue Chatswood, NSW, Australia Tel. no. +612 94249999 Fax no. +612 94249944 colin.chan@vgaustralia.com I t is terrific to see this promising research by Dr. Waring and his group on ion diffusivity with the aim of improving our understanding of the exact effects of collagen crosslinking on the cornea. While Wollensak and Seiler’s pioneering work established the increase in stress strain properties, increased resistance to hydration and enzymatic digestion as well as the clinical effectiveness of collagen crosslinking, still many questions about crosslinking remain. While an effective procedure, there is great room for potential improvement in refining the procedure to reduce risk for our patients while achieving maximum benefit. For example, it is not known whether the amount of crosslinking induced by the traditional Dresden protocol with epithelium-off crosslinking is more than what is required to stabilize the cornea. It may be also possible to alter the delivery pattern of crosslinking to maximize the change in keratometry and flattening of the cone. The effectiveness of different methods of crosslinking such as epithelium-on methods and accelerated crosslinking is another unanswered question. And there is poor understanding of the parameters for expanding indications for crosslinking such as treatment of microbial keratitis, corneal edema, and treatment of mild cases of keratoconus with crosslinking and PRK. Hopefully, Dr. Waring’s future studies on ion diffusivity will help us answer these questions. Editors’ note: Dr. Chan has no financial interests related to his comments. Dr. Waring and his team performed standard Dresden protocol epithelial-off crosslinking with riboflavin and UVA light on fresh, intact porcine eyes. Control eyes received riboflavin without irradiation. They measured ion diffusivity in the x-y plane using fluorescence recovery after photobleaching (FRAP), where a region of tissue is bleached and a fluorescent probe diffuses into it. Diffusivity of the probe (riboflavin in this case) is then calculated based on the speed of fluorescent recovery. The researchers evaluated diffusivity through the cornea in the z direction through an indirect method, using a custom-made chamber to measure electrical conductivity through the tissue. Results Results showed that crosslinking induced statistically significant changes to ion diffusivity through the corneal continued on page 52